Decapeptide-12 Modulation of Sirtuin Gene Expression in Epidermal Keratinocyte Progenitors

Abstract

Recent reports detail the pleiotropic roles sirtuins play in repressing premature aging, delaying cellular senescence, enhancing longevity, and ameliorating a wide range of aging disorders. Herein, we report our findings on the potent sirtuin activator, decapeptide-12, and compare its performance to the well documented oxyresveratrol. Treatment of human epidermal keratinocyte progenitors with 100 μM decapeptide-12 increased transcription of SIRT1 by 141±11 percent relative to control cells, whereas levels of SIRT3, SIRT6, and SIRT7 were increased by 121±13 percent, 147±8 percent and 95.4±14 percent, respectively. Decapeptide-12 upregulated sirtuin transcription to similar levels as oxyresveratrol but with reduced cytotoxicity.

What is claimed is: 
     
         1 . A peptide consisting of SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, or SEQ. ID NO: 12. 
     
     
         2 . The peptide of  claim 1  wherein the peptide consists of SEQ ID NO: 9 modified by a modifying group, the modifying group being either a palmitoyl group or an acetyl group at an amino-terminal end, or amidation of a carboxy-terminal end, or both. 
     
     
         3 . The peptide according to any of  claims 1 - 2  consisting of SEQ ID NO: 11 having a tyrosine amino acid at a position 6 as a D-isoform, and all other amino acids being L-isoforms. 
     
     
         4 . A composition comprising a first peptide consisting of SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, or SEQ. ID NO: 12. 
     
     
         5 . The composition of  claim 4  wherein the peptide consists of SEQ ID NO: 9 modified by a modifying group, the modifying group being either a palmitoyl group or an acetyl group at an amino-terminal end, or amidation of a carboxy-terminal end, or both. 
     
     
         6 . The composition according to any of  claims 4 - 5  consisting of SEQ ID NO: 11 having a tyrosine amino acid at a position 6 as a D-isoform, and all other amino acids being L-isoforms. 
     
     
         7 . The composition according to any of  claims 4 - 6  wherein the peptide is present in a concentration of 1 μm or greater. 
     
     
         8 . A method of treating a subject by modulating expression of a sirtuin gene in a skin cell to reduce symptoms of skin aging, the method comprising administering to a subject in need thereof a composition comprising an effective amount of one or more peptides, wherein the one or more peptides consist of, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, or SEQ. ID NO: 12. 
     
     
         9 . The method according to  claim 8  wherein the peptide consists of SEQ ID NO: 9 modified by a modifying group, the modifying group being either a palmitoyl group or an acetyl group at an amino-terminal end, or amidation of a carboxy-terminal end, or both. 
     
     
         10 . The method according to any of  claims 8 - 9  wherein the peptide consists of SEQ ID NO: 11 having a tyrosine amino acid at a position 6 as a D-isoform, and all other amino acids being L-isoforms. 
     
     
         11 . The method according to any of  claims 8 - 10  wherein the skin cell is a progenitor. 
     
     
         12 . The method according to  claim 11  wherein the progenitor is an epidermal keratinocyte progenitor, a melanoblast, a fibroblast, a histioblast, or a dendroblast. 
     
     
         13 . The method according to any of  claims 8 - 10  wherein the skin cell is terminally differentiated. 
     
     
         14 . The method according to  claim 13  wherein the skin cell is a keratinocyte, a melanocyte, a fibrocyte, a histiocyte, or a dendrocyte. 
     
     
         15 . The method according to any of  claims 8 - 14  wherein the peptide is present in a concentration of 1 μm or greater. 
     
     
         16 . The method of according to any of  claims 8 - 15  wherein the sirtuin gene comprises SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7. 
     
     
         17 . The method according to any of  claims 8 - 16  wherein the composition further comprises oxyresveratrol. 
     
     
         18 . The method according to any of  claims 8 - 17  wherein the skin cell is a mammal cell. 
     
     
         19 . The method according to  claims 18  wherein the skin cell is human. 
     
     
         20 . A method of modulating expression of a sirtuin gene in a skin cell, the method comprising administering to a subject in need thereof a composition comprising an effective amount of one or more peptides, wherein the one or more peptides consist of, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, or SEQ. ID NO: 12.